title: CIP2A influences survival in colon cancer and is critical for maintaining Myc expression.
abstract: The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.
authors.affiliation: Department of General, Visceral, Vascular and Paediatric Surgery (Department of Surgery I), University Hospital Wuerzburg, Wuerzburg, Germany ; Department of Biochemistry and Molecular Biology, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Wiegering
authors.forename: Christina
authors.initials: C
authors.lastname: Pfann
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Uthe
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.forename: Lukas
authors.initials: L
authors.lastname: Rycak
authors.forename: Uwe
authors.initials: U
authors.lastname: Mäder
authors.forename: Martin
authors.initials: M
authors.lastname: Gasser
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Waaga-Gasser
authors.forename: Martin
authors.initials: M
authors.lastname: Eilers
authors.forename: Christoph-Thomas
authors.initials: CT
authors.lastname: Germer
mesh_terms: D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011184:Postoperative Period; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D001324:Autoantigens; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C489427:MYC protein, human; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D020930:MAP Kinase Kinase Kinases